1. Field of the Invention
This invention relates to naturally-occurring thiophenes, acetylenes and synthetic, structurally-related derivatives, analogues or acetylenic compounds, to compositions containing such compounds, and to the use of such compositions as insert control agents with a novel phototoxic mode of action.
2. Description of the Prior Art
It is now well known that many hyrocarbon compounds containing non-heterocyclic groups therein thave pesticidal activity and can provide pesticidal compositions. Among the patents which disclose such compounds, and that use, are the following Canadian Patents: 508,018, 675,157, 720,767, 734,397, 843,918, 869,518 and 1,028,945. However, many of such pesticides are neurotoxins, with the result that many insects develop resistance thereto.
The novel phototoxic mechanism of thiophenes and related acetylenes is a means of overcoming this resistance problem. Phototoxicity involves the absorbtion of light by the sensitizer molecule (thiophene or acetylene) and subsequent reaction of the sensitizer in its excited state causing deleterious biological effects. Discovery of the phototoxic effects of thiophenes to nematodes were first reported by F. Gommers (1972, Nematalogical 18, 458) and discovery of the phototoxic effects of polyacetylenes to microorganisms by Towers et al. (1977, Lloydia 40, 487-496).
Early work reports the toxicity of acetylenes and thiophenes to invertebrates without mention of the role of light in the process. For example, U.S. Pat. No. 3,050,442 issued Aug. 21, 1962 to J. D. Bijloo et al, provided a teaching that compositions containing ##STR1## wherein n represents a number selected from the group consisting of 0 and 1, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 each represents substituents selected from the group consisting of hydrogen, methyl propionyl, halogen, nitro, acetyl and phenyl radicals, with the further proviso that when n represents 0, then, R.sub.3 represents, in addition, the thiophene radical and R.sub.2 and R.sub.4 represent only hydrogen. Within such constraints, i.e. when n=1 and R.sub.1 =R.sub.2 =R.sub.3 =R.sub.4 =H, the formula represents the naturally-occurring compound ##STR2## (.beta.-terthienyl). The patentee taught that such a compound would have pesticidal effects and could be used for combatting insect pests.
It has been reported that some naturally-occurring polyacetylenes and their thiophene derivatives are toxic to invertebrates. Thus, it has been reported that cis-dehydromatricaria ester isolated from Solidago altimissa, and tridec-1-ene-3,5,7,9,11-pentyne isolated from Xanthium canadense (see S. Nakajima et al, 1977, Agric. Biol. Chem., 41, 1801-1805) both of which are widely distributed in the Asteraceae, are ovicidal to the fruit fly Drosophila melanogaster and the house fly, Musca domestica. Several polyacetylenes, e.g., .alpha.-terthienyl from Tagetes spp. (see A. R. Verhagen et al. 1974 Arch. Dermatol, 110, 441) and two isomeric polyacetylenes from Carthamus tinctorium (see S. Kogiso et al, 1976 Agric Biol. Chem. 40, 2085-2089) have been found to be nematocidal.
It has also been taught (see D. McLachlan et al, 1982, Experimentia, 38, 1061-1062) that 1-phenylhepta-1,3,5-triyne (PHT), a polyacetylenic compound isolated from Bidens pilosa L. (Asteraceae) has antifeedant properties towards larvae of the polyphagous insect Eaxoa messoria.
Recent work has demonstrated that the toxicity of polyacetylenes and thiophenes to insects is greatly enhanced by sources of radiation in the range 300-400 nm. Nine of 14 substances tested were phototoxic to mosquito larvae of Aedes aeqyptii at 500 ppb (C. K. Wat et al, 1981, Biochem. Syst.& Ecol. 9, 59-63), yet had no effect at this concentration in the dark. The exceptional phototoxicity of two compounds. .alpha.-terthienyl and 2-(non-trans en-3',5', 7'-triynyl) furan were subsequently reported (J. T. Arnason et al, 1981, Biochem. Syst. & Ecol. 9, 63-69). Analogues and derivatives of these compounds were also found to be toxic to mosquito larvae (J. T. Arnason et al, 1986, Phytochem., in press and J. Kagan et al. 1983 Insect Sci. App. 4, 377-381). Large scale synthesis of .beta.-terthienyl permitted field trials in natural breeding pools of mosquito larvae that have demonstrated that good control can be achieved at applications of 100 g active ingredient/ha. with acceptable non target effects. (Philogene et al. 1985, J. Econ. Ent. 78, 121 and 1986, J. Chem. Ecol. in press).
With insects other than mosquito larvae, there are reports of the phototoxicity of .alpha.-terthienyl to larvae of Manduca sexta (K. Downum et al, 1984Pest. Biochem. Physiol. 22, 104) and to larvae of Euxoa messoria (D. Champagne et al, 1984 Experientia, 40, 577. J. Kagan et al, 1983, Experimentia, 39, 402-403) reported photoovicidal activity several substances to Drosophila melanaogaster.
D. E. Champagne et al. in Journal of Chemical Ecology Vol. 12 No. 4, 1986 p 835, discloses the effect of the following seven structures on three species of herbivorous insects: a monothiophene, a bithiophene, .alpha.-terthienyl, phenylheptatriyne, phenylheptadiynene, phenylheptadiynene acetate and matricaria lactone. It was taught that the biosynthetically derived thiophenes were more toxic than their acetylene precursors and that toxicity increased with increasing number of thiophene rings for this series. ##STR3##
Towers et al, in Canadian Patent No. 1,173,743 patented Sept. 4, 1984, provided a method for protecting plants from herbivores and pathogens, by applying, to the plants, a composition comprising an inert carrier and a biocidal-amount of a conjugated polyacetylene; and subjecting the composition, when on those plants, to UV radiation in the range of 300 nm to 400 nm. That patent also provided a pesticidal composition comprising an inert carrier and an amount of a conjugated polyacetylene which, when applied at a rate of 0.1 lb/acre to a plant, and then subjected to UV radiation in the range of 300 nm to 400 nm, had pesticidal activity. The conjugated polyacetylenes taught therein could be one or more of the following:
1-phenylhepta-1,3,5-triyne, PA0 [5-(but-3-en-1-ynyl)] 5'-methyl .alpha.-bithiaine methyl-4-methythiodeca-2,4-dien-6,8-diyn-1-oate, PA0 methyldodeca-cis.-2,8,10-trien-4,6-diyn-1-oate, PA0 (2.sup.1 -phenylethyl)-undeca-2,4-dien-8,10-diyn-1-carboxamide, PA0 dodec-1-en-3,5,7,9,11-pentayne, PA0 2-(but-3'-yn-2'-onylidenyl)-5-pentyl-tetrahydropyran, PA0 3-[prop-1-yne]-6-(hexa-3'3'-dien-1-ynyl)-1,2-dithianine, PA0 2-(3'-buten-1-ynyl)-5-(3'-penten-1-ynyl)-thiophene, PA0 .gamma.-(2'-neuynylidenyl)-.gamma.-but-2-enyrolactone, PA0 1-acetoxytetradeca-4,6,12-trien-8,10-diyne, PA0 tetradeca-4,6-dien-8,10,12-triynyl-sec-butenoate, 1,2-dihydroxytrideca-3,5-dien-7,9,11-triyne, PA0 2-(non-trans-1'-en-3',5',7'-triynyl)-tetrahydropyran, PA0 2-(non-trans-en-3',5'7'-triynyl)-furan, PA0 heptadeca-1,9,6-trien-4,6-dien-3-one, PA0 1,3-dihydroxytetradeca-4,6,12-trien-8,10-diyne, PA0 1-hydroxy-7-phenylhepta-2-en-4,6-diyne, PA0 2chloro-1-hydroxytrideca-3,11-dien-5,7,9-triyne PA0 7-phenylhepta-2-en-4,6-diynal, PA0 .gamma.-(hex-4'-en-2'-ynylidenyl)-.gamma.-but-2-enyrolactone, PA0 heptadeca-1,8,15-trien-11,13-diyne, PA0 nonadeca1,7,9,17-tetraen-11,13diyne, PA0 3,4-dihydroxytrideca-1,5,11-trien-7,9-diyne, PA0 trideca-1,3,5,11-tetraen-7,9-diyne, PA0 1,2-dihydroxytrideca-3,11-dien-5,7,9-triyne, PA0 1-hydroxytetradeca-6,8,11,13-tetraen-10-yne, PA0 1-acetoxytetradeca-6,8,12,14-tetraen-10-yne, PA0 1,3-dihydroxytetradeca-trans, trans-4,6-dien-8,10,12-triyne. PA0 1,3-diacetoxytetradeca-4,6-dien-8,10,12-triyne, PA0 tetradeca-1,8,13-trien-4,6-diyn-3-one, PA0 1-hydroxy-7-phenylhepta-2,4,6-triyne, PA0 7-phenylhepta-2,4,6-triynal; PA0 5-acetoxy-7-(penta-2',4'-diynylidenyl)-2,6-dioxa-(4,4-spiro-nona-3,8-diene) ; PA0 1-[5'-pentyl-3',4',5',6'-tetrahydrophyranilidenyl]-but-3-yne-2-one; and PA0 (3-hydroxy-2-[trans-1'-nonen-3,5,7-trynyl]-tetrahydropyran. PA0 #1=K. TAmao et. al., Tetrahedron, Vol. 38 #22, 3347-3354, (1982). PA0 #2=Reference given in B. J. R. Philogene, et. al., Journal of Economic Entomology, Vol 70 #1 pp 121-126, (1985). PA0 #3=J. W. Sease and L. Zechmeister, J. Am. Chem. Soc 69, 270, (1947). PA0 #4=A. Meuller et. al., Acta Chem Acad Sci Hung, 52, 261 (1961) Chem Abstr, 67, 64222 (1967). PA0 #5a=J. H. Uhlenbroek and J. D. Bijloo, Rec Trav Chim, 79, 1181-96, (1960) Eng. PA0 #5b=H. J. Bestmann and W. Schaper, Tetrahed, Letters, No. 3, pp 243-244 (1979). PA0 #6=J. Kagan, et. al., J. Org. Chem., 48, 4076-4078, (1983). PA0 #7=H. Wynberg et. al., J. Am. Chem. Soc. 79, 1972 (1957) PA0 #8=F. Bohlmann et. al., Chem. Ber. 99, (3), 984, (1966). PA0 #9=H. Wynberg et. al., J. Am. Chem. Soc., 82, 1447, (1960). PA0 #10=K. E. Schulte et. al., Arch. Pharm. 296, 456, (1963). PA0 #11=M. Sy et. al., J. Chem. Soc., 1975, (1954). PA0 #12=CA 55: p 1800 2d. PA0 #13=CA 58: P4991a. PA0 #14=H. Wynberg et. al., J. Am. Chem. Soc., 89, #14, 3487-94. (1967). PA0 #15=A. Carpita, R. Rossi, and C. Veracini, Tetrahedron Vol. 41, #1, pp 1919-1929, (1985). PA0 #16=P. Riberreau, G. Quequiner and P. Pastour, Bull. Soc. Chim. Fr., 4, pp 1581-7, (1972). PA0 #17=J. Mejer, W. Chodkiewicz, P. Cadiot, and A. Willemart, Compt, Rend. 245, 1634, (1957). PA0 #18=Patented by I. Arnason et al. Canadian Patent No. 1,169,767. and Canadian Patent No. 1,173,743. PA0 #19=Commercially available PA0 #20=P, Chauvin, J. Murel, P., Pastour and J. Martinez, Bull. Soc. Chim. Fr. (9-10 pt 2) pp 2079-85. (1974). PA0 #21=P. Raymond, Compl. Rend. 202. pp 854-6, (1936) PA0 #22=E. Campaigne, and L. Fedor, Journal of Heterocyclic Chem, 1 (5), pp 242-4, (1964). PA0 #23=R. E. Atkinson, R. F. Curtis and J. A. Taylor, J. Chem, Soc. (C) 7, pp 578-82, (1967). PA0 #24=R. E. Atkinson, R. F. Curtis And G. T. Philips, Chem. Ind, 51, pp 2101-2102, (1964). PA0 #25=CA 96: P117583r; CA 96 P16085z. PA0 #26=F. Bohlmann et al, Tett. Lett, (19) pp 1385-8, (1965).
Other compounds which are structurally related to the above discussed compounds which have been disclosed in the scientific literature are these listed in the following Table 1.
TABLE 1 __________________________________________________________________________ COMPOUND DISCLOSED IN (FORMULA) COMPOUND NO. REFERENCE NO. __________________________________________________________________________ The following fourteen compounds of Formula I: FORMULA I ##STR4## 1. R.sup.1 = R.sup.2 = Br 2. R.sup.1 = R.sup.2 = CH.sub.3 3. R.sup.1 = R.sup.2 = CO.sub.2 H 4. R.sup.1 = R.sup.2 = CO.sub.2 CH.sub.3 5. R.sup.1 = R.sup.2 = C(CH.sub.3).sub.3 #2, #3 and #5 #3, #12, #13 #6 #6 #11 6. R.sup.1 = CH.sub.3 ; R.sup.2 #3H 7. R.sup.1 = CO.sub.2 H; R.sup.2 #6H 8. R.sup. 1 = CO.sub.2 CH.sub.3 ; R.sup.2 = #6 9. R.sup.1 = tritium; R.sup.2 = COCH.sub.3 #8 10. R.sup.1 = R.sup.2 = COCH.sub.3 #8, #9 11. R.sup.1 = R.sup.2 = C.sub.6 H.sub.5 #10 12. R.sup.1 = CH.sub.2 OH; R.sup.2 #11 13. R.sup.1 = Br; R.sup.2 = H #12 and #13 14. R.sup.1 = CHO; R.sup.2 = H #6 FORMULA II ##STR5## 15. #1 and #4 The following four compounds of Formula III: FORMULA III ##STR6## 16. R.sup.1 = R.sup.2 = R.sup.3 = R.sup.4 = R.sup.5 = R.sup.6 = CH.sub.3 ; R.sup.7 = H 17. R.sup.1 = R.sup.2 = R.sup.5 = R.sup.6 = R.sup.7 = H; R.sup.3 = R.sup.4 = CH.sub.3 18. R.sup.1 = R.sup.2 = R.sup.5 = R.sup.6 = R.sup.7 = CH.sub.3 ; R.sup.3 = R.sup.4 = H 19. R.sup.1 = R.sup.4 = R.sup.6 = R.sup.7 = H; R.sup.2 = R.sup.3 = R.sup.5 = CH.sub.3 #5 #5a and 5b #5 #5 FORMULA IV ##STR7## 20. #5 and #7 FORMULA V ##STR8## 21. R.sup.1 = R.sup.2 = R.sup.3 = R.sup.4 = tritium #8 FORMULA VI ##STR9## 22. #5a FORMULA VII ##STR10## 23. #14 FORMULA VIII ##STR11## 24. #7 The following two compounds of Formula IX: FORMULA IX ##STR12## 25. R.sup.1 = H; R.sup.2 = Br 26. R.sup.1 = R.sup.2 = Br #15 #15 FORMULA X ##STR13## 27. #16 FORMULA XI ##STR14## 28. #17 and #18 FORMULA XII ##STR15## 29. #19 FORMULA XIV ##STR16## 30. #20 FORMULA XV ##STR17## 31. #24 and #25 FORMULA XVI ##STR18## 32. #21, #22 and #23 FORMULA XVII ##STR19## 33. #18 FORMULA XVIII ##STR20## 34. #26 __________________________________________________________________________
In the above table, the references identified as numbers 1-28 are as follows:
Nevertheless, it is well established that the biological activity of naturally-occurring thiophenes and acetylenes and synthetic, structurally-related derivatives, analogues or acetylenic compounds is not predictable. Moreover, such naturally-occurring thiophenes, acetylenes and synthetic, structurally-related derivatives, analogues or acetylenic compounds, to be biologically useful, should also be relatively stable but should leave no toxic residue, and such characteristics are also not predictable. Accordingly, it is an object of this invention to provide novel phototoxic, naturally-occurring thiophenes, acetylenes, or synthetic, structurally-related derivatives, analogues or acetylenic compounds which have a selected balance between stability and biodegradability and consequently have improved utility as insect control agents.
It would also be desirable, and it is also an object of this invention, to provide pesticidal compositions containing phototoxic, naturally-occurring thiophenes, acetylenes, or synthetic, structurally-related derivatives, analogues or acetylenic compounds, in which such phototoxic, naturally-occurring thiophenes, acetylenes or synthetic, structurally-related derivatives, analogues or acetylenic compounds are relatively stable but which are eventually biodegradable and would therefore leave no long-lived toxic residues.
It would also be desirable, and it is therefore yet another object of this invention to provide methods for insect control involving the use of phototoxic, naturally-occurring thiophenes, acetylenes, or synthetic, structurally-related derivatives, analogues or acetylenic compounds which are relatively stable but which are eventually biodegradable and generally would leave no long-lived toxic residues.